methyl 2-(3,4-methylenedioxyphenyl)butyrate | 148149-44-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: methyl 2-(3,4-methylenedioxyphenyl)butyrate
• 英文别名: Methyl 2-(1,3-benzodioxol-5-yl)butanoate；methyl 2-(1,3-benzodioxol-5-yl)butanoate
• CAS: 148149-44-4
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: KRONJCNXRLLFHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(3,4-methylenedioxyphenyl)butyrate 、 3-甲基-4-硝基苯甲酸 在 磷酸酐 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 以56%的产率得到methyl 2-[4,5-methylenedioxy-2-(3-methyl-4-nitrobenzoyl)-phenyl]butyrate
  参考文献：
  名称：

  Structure–activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: Identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent

  摘要：

  In the search for AMPA receptor (AMPAR) antagonists, 2,3-benzodiazepines represent a family of specific noncompetitive antaaonists with anticonvulsant and neuroprotective properties. We have previously shown that 2,3-benzodiazepin-4-ones possess marked anticonvulsant properties and high affinity for the noncompetitive binding site of the AMPAR complex. In this paper, we report the synthesis and pharmacological characterization of a full set of 2,3-benzodiazepin-4-ones in order to better define the structure-activity relationship (SAR) of this class of compounds. Binding assays and functional tests were performed to evaluate the antagonistic activity at the AMPARs. Through these results we have identified a potent AMPAR antagonist, 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (5c). This compound noncompetitively inhibited AMPAR-mediated toxicity in primary mouse hippocampal cultures with an IC50 of 1.6 mu M and blocked kainate-induced calcium influx in rat cerebellar granule cells with an IC50 of 6.4 mu M. Thus, 5c has the in vitro potential as therapeutic drug in the treatment of various neurological disorders. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.080
• 作为产物：
  描述：

  苯并[1,3]二氧代l-5-乙酸甲酯 、 碘乙烷 在 potassium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以85%的产率得到methyl 2-(3,4-methylenedioxyphenyl)butyrate
  参考文献：
  名称：

  Structure–activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR antagonists: Identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent

  摘要：

  In the search for AMPA receptor (AMPAR) antagonists, 2,3-benzodiazepines represent a family of specific noncompetitive antaaonists with anticonvulsant and neuroprotective properties. We have previously shown that 2,3-benzodiazepin-4-ones possess marked anticonvulsant properties and high affinity for the noncompetitive binding site of the AMPAR complex. In this paper, we report the synthesis and pharmacological characterization of a full set of 2,3-benzodiazepin-4-ones in order to better define the structure-activity relationship (SAR) of this class of compounds. Binding assays and functional tests were performed to evaluate the antagonistic activity at the AMPARs. Through these results we have identified a potent AMPAR antagonist, 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (5c). This compound noncompetitively inhibited AMPAR-mediated toxicity in primary mouse hippocampal cultures with an IC50 of 1.6 mu M and blocked kainate-induced calcium influx in rat cerebellar granule cells with an IC50 of 6.4 mu M. Thus, 5c has the in vitro potential as therapeutic drug in the treatment of various neurological disorders. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.080